Ketosis
In periods of fasting, extreme exercise, and/or low carbohydrate consumption, glucose and glycogen stores in the body are rapidly used and can become quickly depleted. Failure to replenish glucose stores as they become depleted causes the body to metabolically shift to the creation of ketone bodies for energy. This metabolic state is called “ketosis”.
Ketone bodies can be used by cells of the body as a fuel in addition or instead of glucose to satisfy the body's energy needs, including the brain and heart. During prolonged fasting, for example, blood ketone levels can increase to 2-3 mmol/L or more. It is conventionally understood that when blood ketones rise above 0.5 mmol/L, the heart, brain and peripheral tissues are using ketone bodies (e.g., beta-hydroxybutyrate and acetoacetate) as the primary fuel source. This condition is referred to as ketosis. Between 1.0 mmol/L and 3.0 mmol/L the condition is called “nutritional ketosis.”
Upon transitioning into ketosis, or in other words, during ketogenic metabolism in the liver, the body uses dietary and bodily fats as a primary energy source. Consequently, once in ketosis, one can induce loss of body fat by controlling dietary fat intake and maintaining low carbohydrate intake to maintain a ketogenic metabolic state.
While in ketosis, the body is essentially burning fat for its primary fuel. The body initially cleaves fats into fatty acids and glycerol. It then transforms fatty acids into acetyl coenzyme A (“acetyl-CoA”) molecules, which are then eventually transformed through ketogenesis into the water-soluble ketone bodies beta-hydroxybutyrate (“β-hydroxybutyrate” or “BHB”), acetoacetate, and acetone in the liver. BHB and acetoacetate are the ketone bodies used by the body for energy while acetone is removed as a by-product of ketogenesis. Although BHB is technically not a ketone, it is still referred to as a “ketone body” in the context of ketosis.
The metabolism of ketone bodies is associated with several beneficial effects. However, despite the many health advantages of pursuing a ketogenic diet or lifestyle and maintaining a state of nutritional ketosis, there remain significant barriers to pursuing and maintaining a ketogenic state. One of these barriers is the difficulty of transitioning into a ketogenic state. The fastest endogenous way to entering ketosis through depleting glucose stores in the body is through fasting combined with exercise. This is physically and emotionally demanding and is extremely challenging even for the most motivated and disciplined.
Additionally, the transition into ketosis is often accompanied by hypoglycemia which can cause lethargy and light-headedness in many, resulting in an uncomfortable physiological and mental state commonly referred to as the “low-carb flu” or “keto flu.” In addition, many people experience a down regulation in their metabolism as the body goes into an “energy-saving” mode. Some suggest that these transitory symptoms may last as long as two to three weeks. During this transition period, if any meal or snack consisting of carbohydrates over the restrictive amount is consumed, there is a rapid termination of ketogenesis, causing the body to exit from its state of ketosis as the body shifts back to glucose utilization as its primary fuel. At this point, the difficult transition into ketosis must begin anew. Thus, despite the potential of a ketogenic diet for weight loss and other health benefits, serious limitations continue to hinder the full realization of its potential.
Cannabidiol
Cannabidiol (CBD) is one of the major cannabinoid constituents of the cannabis plant. Unlike tetrahydrocannabinol (THC), another major cannabinoid constituent of the cannabis plant, CBD does not have psychoactive effects. CBD is believed to have a counteractive effect on some of the negative effects of THC such as anxiety and disordered thinking. CBD is typically the second most abundant constituent of cannabis flowers/buds and the highest constituent of most other portions of the plant. It can account for up to 40% of the plant's extract.
CBD is currently used as an active ingredient in medicines intended to alleviate pain, particularly pain associated with multiple sclerosis, and in anti-seizure medicines intended to treat epilepsy. CBD is most commonly administered orally or via inhalation. CBD is believed to interact with a variety of biological targets, including cannabinoid receptors of the endocannabinoid system (ECS) and neurotransmitter receptors.
Though CBD has several positive uses and appears to be a promising drug agent, with other uses likely to be discovered in the future, some limitations to its use are currently known to exist. Use of CBD is associated with undesirable side effects such as light-headedness, general fatigue and malaise, and sleep disruption (see, e.g., Murillo-Rodriquez et al. “The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent” Behav. Neurosci. 2008 December, 122(6): 1378-82; and “Epidiolex” FDA Label, available at fda.gov). Thus, despite benefits associated with CBD as a supplement or drug, several limitations to its use remain.